Flexibletransmembrane helices frequently support the conformationaltransitions between different functional states of membrane proteins.While proline is well known to distort and destabilize transmembranehelices, the role of glycine is still debated. Here, we systematicallyinvestigated the effect of glycine on transmembrane helix flexibilityby placing it at different sites within the otherwise uniform leucine/valinerepeat sequence of the LV16 model helix. We show that amide deuterium/hydrogenexchange kinetics are increased near glycine. Molecular dynamics simulationsreproduce the measured exchange kinetics and reveal, at atomic resolution,a severe packing defect at glycine that enhances local hydration.Furthermore, glycine alters H-bond occupancies and triggers a redistributionof α-helical and 310-helical H-bonds. These effectsfacilitate local helix bending at the glycine site and change thecollective dynamics of the helix.
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